P1099: THE SPECTRUM OF SECOND PRIMARY MALIGNANCIES AND CAUSE-SPECIFIC MORTALITY AMONG PATIENTS WITH FOLLICULAR LYMPHOMA IN THE UNITED STATES: A POPULATION-BASED STUDY.
Authors: K. Chamarti, V. Rudraraju, S. Kiani
Journal: HemaSphere (2022)

Background: Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). FL accounts for 35 percent of NHLs and has an estimated incidence of 3.18 cases per 1,00,000 people in the United States. The clinical course of FL is variable, and it has median overall survival of 10 to 12 years. In the era of targeted therapies with anti-CD20 antibodies, there is data lacking on the spectrum of second primary malignancies (SPMs) and cause-specific mortality in patients with follicular lymphoma. Aims: In the current study, we aim to identify the risk of SPM and cause specific mortality in FL patients in the era of targeted therapies with anti CD-20 antibodies using a national registry from the United States. Methods: Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-18, we conducted a retrospective study with patients diagnosed with FL (ICD-0-3 code 9690/3) between 2012 and 2018. We calculated the risk of SPMs developing ≥ 2 months using standardized incidence ratios (SIRs) and cause-specific mortality by standardized mortality ratios (SMRs) and absolute excess risk (AER)/10,000 population. Results: A total of 6,215 patients with follicular lymphoma (FL) were included in this study. The median age at diagnosis was 66 years (range 3 to 85 years) and the median follow-up duration was 31 months (range 0 to 81 months). A total of 355 patients (5.7%) developed 376 SPMs, of which 56% were solid organ malignancies, and 44% were hematologic neoplasms. The latency period for SPM development was 20 months (range 2 to 80 months). The SPM risk for the cohort was significantly elevated (SIR= 1.99, 95% confidence interval [CI] = 1.79-2.2, P<0.05) when compared with the general population. The SIR was higher in females (SIR= 2.16, 95% CI=1.85-2.51) when compared to males (SIR= 1.86, 95% CI= 1.61- 2.13). The SIR for age groups were as follows: age < 65 years (SIR= 2.84, 95% CI= 2.43-3.31), age > 65 years (SIR= 1.59, 95% CI= 1.38-1.82). The risk for hematopoietic SPMs was higher (SIR= 8.66, 95% CI= 7.33-10.15) than solid organ tumors (SIR= 1.30, 95% CI= 1.13-1.49). Specific SPMs with the highest risk included NHL (SIR= 16.24, 95% CI= 13.62-19.22), Hodgkin lymphoma (SIR= 14.31, 95% CI= 5.25-31.15), followed by thyroid cancer (SIR= 4.63, 95% CI= 2.53-7.76), kidney and renal pelvis cancer (SIR= 1.43, 95% CI= 1.55-4.14), and lung cancer (SIR= 2.16, 95% CI= 1.63-2.79). The risk of developing Hodgkin lymphoma, thyroid, and kidney cancers was high in the first year of FL diagnosis. While, the risk for NHL was elevated throughout the follow-up period. At last follow-up, 724 (11.5%) patients had died, of which 65% were due to malignant neoplasms. The risk of mortality due to all malignant cancers combined was statistically significant (SMR= 6.26, 95% CI= 2.00-2.31), largely due to mortality from NHL (SMR= 139.5, 95% CI= 126-154, AER= 286.8), leukemia (SMR= 5.23, 95% CI= 2.99-8.49, AER= 9.63), and infectious diseases (SMR= 2.58, 95% CI= 1.04-5.31, AER=3.19). Summary/Conclusion: Our study reveals that despite therapeutic advances in FL, hematologic neoplasms (including NHL and leukemia) remain the major cause of death in our cohort. Patients with FL are at higher risk of SPM than the general population, most notably for NHL, Hodgkin lymphoma, followed by thyroid, kidney, and lung cancer. These patients may benefit from cancer-specific screening during follow-up.